| Objective This study was designed to examine dynamicly the expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and their receptors (NPR-A,NPR-C), and to explore the role of natriuretic peptide system in the occurrence and development of the primary hypertension.Methods Male SHR(n=48)were randomly subjected to six groups by age:4-week-old group, 8-week-old group, 12-week-old group, 18-week-old group, 24-week-old group and 30-week-old group respectively. Same sex and age matched Wistar-Kyoto Not motensive rat(WKY) served as control. Blood pressure was measured. Kidney mass index (KMI)was measured on the base of that kidney weight is relative to body weight. Morphological characteristics were evaluated with HE, PAS and situs red staining. Glomerulus mesangial matrix relative area, renal interstitial collagen relative area, mean glomerular volume were assessed with computer-assisted image analysis system (Image-ProPlus, Version: 6.0); Plasma and renal homogenate concentration of ANP,BNP, were measured by enzyme-linked immunosorbent assay (ELISA). The expression and distribution of NPR-A, NPR-C in kidney were examined by immunohistochemistry combined with computer image technology. The protein levels of NPR-A, NPR-C in kidmey were determined further by Western blot. The transcription level of natriuretic peptides (ANP,BNP) were evaluated by real time polymerase chain reaction (RT-PCR).Results1. SBP, KHI: Compared with age-matched WKY, SBP of SHR in 8w, 12 w, 18w,24w,30w was all significantly much higher (P<0.01). Compared with age-matched WKY, KMI of SHR in 8w, 12 w, 18w,24w,30w was all significantly much higher(P<0.01).2. Morphological characteristics: Compared with age-matched WKY, both the mean glomerular volume and relative area of glomerulus mesangial matrix of SHR in12,18, 24,30 week were significantly much higher (P<0.01). Collogen-relative-area of SHR in18,24,30week was all significantly much higher than that of WKY in the corresponding week age(P<0.01).3. The level of plasma and renal homogenate concentration of ANP,BNP and their mRNA(1) The plasma level of ANP,BNP: With the increase of age (from 4w to 30w), the plasma level of ANP in SHR group and WKY group showed no significant difference(P>0.05), but the plasma level of BNP of SHR group showed an age-dependent increase and was much higher than that of age-matched WKY(P<0.05).(2) With the increase of age (from 4w to 30w), the level of ANP and BNP in kidney tissues of SHR first descended and then rose, while the level of ANP and BNP in kidney tissues of WKY gradually rose. The level of ANP in kidney tissue of SHR group of 8w, 12 w, 18w,24w,30w was significantly lower than that of age-matched WKY(P<0.05). Compared with age-matched WKY, the renal level of SHR of 4w was much higher(P<0.05), but the level of BNP in kidney tissue of SHR group of 8w, 12 w, 18w was significantly lower than that of age-matched WKY(P<0.05). The level of BNP in kidney tissue of SHR group of 24w, 30 showed no significant difference(P>0.05).(3) the transcription level of ANP, BNP in kidney tissues: With the increase of age (from 4w to 30w), the transcription level of ANP, BNP mRNA in kidney of SHR group and WKY group descended gradually. Compared with age-matched WKY, the transcription level of ANP, BNP in kidney of SHR of 4w was much higher(P<0.05), but the transcription level of ANP, BNP in kidney of SHR of 8w,12w,18w,24w,30w both was much lower(P<0.05).4. the protein expression of NPR-A,NPR-C in kidney tissues: With the increase of age (from 4w to 30w), the expression of NPR-A and NPR-C protein in kidney of SHR group both were descreased gradually(P<0.05). Compared with age-matched WKY, the expression of NPR-A in kidney of SHR of 4w,8w was much higher(P<0.01), but the expression of NPR-A in kidney of SHR of 12w,18w,24w,30w was much lower(P<0.01), while the expression of NPR-C in kidney of each SHR group was not different from that of each corresponding control groups(P>0.05).Conclusions:1 It was observed that the glomerulosclerosis of kidney of SHR(12 week old-male) was apparent and that renal interstitial fibrosis of kidney of SHR(18 week old-male) was also obvious. Along with the progress of hypertension, the pathological changes mentioned above would turn further aggravated.2 The expression of renal local ANP,BNP possessed with their own characteristic, was not absolutely depends on that of circulatory ANP,BNP.3 In the early stages of hypertension, the expression of renal local ANP,BNP showed compensatively up-regulated or not changed. With the progress of hypertension, the expression of renal local ANP,BNP showed down-regulated in different degree. The result mentioned above demonstrated that reduced expression of renal local ANP, BNP was an important cause of elevation of blood pressure in SHR. 4 In the early stages of hypertension, the expression of renal NPR-A showed compensatively up-regulated compared with age-matched WKY. With the progress of hypertension, the expression of renal local NPR-A and NPR-C in SHR were gradually decreased, but there were no significant differences in the expression of NPR-C in the same age between SHR and WKY. The result above suggested that reduced expression of renal NPR-A played an essential role in the occurrence and development of the primary hypertension even the resulting of renal damage.
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